The majority of immunoglobulin in tears is of the immunoglobulin A (IgA) class, which is produced mainly by plasma cells of the lacrimal gland. The mechanism responsible for the lodging of IgA plasma cells in this gland is unknown and probably not dependent on direct glandular encounter with antigen. Antigen may be recognized by gut-associated lymphoid tissues, with subsequent dissemination of IgA antibody-committed cells to secretory glandular tissue. The proposed investigation will examine glandular factors responsible for preferential lodging of IgA-committed lymphoid cells to rabbit lacrimal and mammary glands (mammary gland offers certain experimental advantages for initial studies). Following initial encounter with antigens by gut-associated lymphoid cells, the effect on the numbers of IgA cells and on their antibody specificity will be examined by direct antigen challenge of glands. It may then be possible to initiate effective local immunity to some infectious agents capable of causing disease of the cornea and conjunctiva. Autografts of lacrimal or mammary gland will be placed into rabbit anterior chambers, a site generally free of antigen. The ability of IgA-committed cells to localize to these grafts and their immediate surrounds both with and without direct antigen encounter will be observed. The production of a glandular factor responsible for differentiation and/or proliferation of IgA-committed lymphoid cells will be examined in tissue culture, and the ability for secretory component, a glandular protein, to effect lodging of IgA-committed cells will be tested. Finally, the ability for gut stimulation with chlorea toxin or E. coli organisms to yield specific IgA antibody in lacrimal gland will be investigated.